Chemicals Linked to Bipolar Psychosis

Posted on March 24, 2014 at 2:55 pm

Researchers have recently discovered a gene that may play a role in the risk of psychosis in individuals with bipolar disorder, called bipolar psychosis.[1] Bipolar disorder is a condition that involves recurrent episodes of mania and depression that are intermixed with euthymic periods, or periods with no depressive or manic symptoms.1 Manic episodes can trigger psychotic symptoms, such as hallucinations and delusions, which are similar to acute psychosis in individuals with schizophrenia.1

This similarity, along with others, propose that the disorders may share a pathophysiology.1 A range of overlapping susceptibility genes for both disorders have also been identified.1 In fact, previous research has shown that a chemical called kynurenic acid (KYNA) exists in higher levels within the cerebrospinal fluid and the prefrontal cortex in individuals who suffer from schizophrenia and bipolar disorder with psychosis.1 Therefore, a team of researchers from the Karolinska Institute in Sweden have looked into the reason behind it.1

“KYNA affects several signaling pathways important to brain function,” said researcher Martin Schalling, MD, PhD. “It is normally produced during inflammation caused by exposure to stress or infection, for example, which themselves have been linked to psychotic episodes.”1

An enzyme called KMO is involved in producing KYNA, and the enzyme’s levels were seen to be significantly reduced in the brains of patients with schizophrenia and bipolar disorder with psychosis.1 Therefore, researchers did further gene analysis on 493 patients with schizophrenia and bipolar with psychosis, as well as 1,044 mentally healthy people.1 They found that among bipolar participants, psychotic episodes were twice as likely if the patient had a gene variant called KMO Arg452.1

In fact, this variant was linked to increased levels of KYNA in the cerebrospinal fluid and levels of KMO in the brain’s hippocampus.1

“Genetic variation in KMO increases the risk for psychotic features in mania of bipolar patients,” the authors of the study write. “This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.”1

Researchers hope that their work will contribute to the future understanding of the link between inflammation and psychosis.1

“Psychosis related to bipolar disease has a very high degree of heredity, up to 80 percent, but we don’t know which genes and which mechanisms are involved,” said Schalling. “This study gives a new explanation that can be linked to signal systems activated by inflammation. This has consequences for diagnostics, and paves the way for new therapies, since there is a large arsenal of already approved drugs that modulate inflammation.”1